Investigation of compression-induced ATP release in head and neck carcinoma

2023 Fiscal Year Final Research Report

• Project/Area Number: 19K10019
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 56070:Plastic and reconstructive surgery-related
• Research Institution: Nippon Medical School
• Principal Investigator: Takada Hiroya 日本医科大学, 医学部, 教授 (30824833)
• Project Period (FY): 2019-04-01 – 2024-03-31
• Keywords: メカノバイオロジー / ATP-Ca2+シグナリング / 振動圧刺激 / ヒト喉頭癌細胞 / K+チャネル開口 / 頭頸部癌

Outline of Final Research Achievements

Mucosal epithelial cells in the head and neck region, which are the passageway for air and food, are repeatedly subjected to mechanical stimuli caused by vocalization and eating, which causes deformation of the cell membrane and cytoskeleton, resulting in mechanical stress within the cells. Therefore, focusing on the head and neck region, which controls functions such as eating and vocalization and is affected daily by mechanical stimuli such as stretching and vocal cord vibration, we measured the response of ATP-Ca2+ signaling to mechanical stimuli and analyzed the relationship with cancer progression due to mechanical stress. A therapeutic strategy was inferred for preventing and inhibiting inflammatory disorders (K+ channel opening inhibition) caused by transient allergic stimuli by histamine in mucosal squamous cell carcinoma cells (KB cells) by activating K+ channels through vibration pressure stimulation.

Free Research Field

形成再建再生医学、細胞生理学、生物物理学、メカノバイオロジー

Academic Significance and Societal Importance of the Research Achievements

頭頸部がんは50歳代から60歳代に診断されることが多く、社会の高齢化に伴って罹患率は増加し、世界では年間約65万人、日本では年間約2万人が発症するとされている。形成外科領域では腫瘍切除と同時に、切除された部分に体の別の部分から皮膚・脂肪・筋肉・骨など（自家組織）を移植して、摂食や発声などの機能を維持できるように再建する。切除するだけでは摂食や発声などに大きな障害が生じ、また術後に顔面に変形が残ることもあり、社会的なハンディキャップを負うばかりか、精神的な障害も引き起こる。日常的な機械刺激が頭頸部がんに与えている影響について、K+チャネルの関与を見出し、治療戦略を示せた意味は大きい。